RESUMEN
The present paper deals with the synthesis of novel macrocyclic complexes of the type [MLX]X, where [(M = Co(II) (1), and Ni(II) (2) X = (Cl2)]. The complexes are synthesized by the reaction of ligand(L)diquinolineno[1,3,7,9]tetraazacyclododecine-7,15-ethane(14H,16H)-benzene with the corresponding metal salts. The synthesized complexes are thoroughly characterized by elemental analysis, FT-IR, 1H-NMR, Mass and electronic spectra. The complexes (1) and (2) were evaluated for in vitro cytotoxicity against human breast adenocarcinoma cell (MCF-7). MTT cytotoxicity studies shows both the complexes are most effective. The binding properties of these complexes with calf thymus-DNA were studied by absorption, emission spectra, viscosity measurements, and thermal denaturation studies. On binding to CT-DNA, the absorption spectrum undergoes bathochromic and hypochromic shifts. The absorption spectral results indicate that the intrinsic binding constant (Kb) are 4.8 × 105 M-1 for (1) and 3.9 × 105 M-1 for (2) respectively, suggesting that complex (1) binds more strongly to CT-DNA than complex (2). The viscosity measurement results revealed the viscosity of sonicated rod like DNA fragments increased when the complex was added to the solution of CT-DNA. The synthesized ligand and its metal complexes are screened for antibacterial and antifungal activities.
Asunto(s)
Antiinfecciosos/síntesis química , Antineoplásicos/síntesis química , Complejos de Coordinación/síntesis química , Compuestos Macrocíclicos/síntesis química , Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/farmacología , Humanos , Sustancias Intercalantes/farmacología , Células MCF-7 , Compuestos Macrocíclicos/farmacologíaRESUMEN
Spirodiazaselenuranes are structurally interesting compounds and the stability of these compounds depends highly on the nature of the substituents attached to the nitrogen atoms. Aromatic substituents are known to play important roles in stabilizing the Se-N bonds in spiro compounds. In this study, several spirodiazaselenuranes are synthesized by introducing benzylic and aliphatic substituents to understand their effect on the stability of the Se-N bonds and the antioxidant activity. Replacement of phenyl substituent by benzyl/alkyl groups significantly reduces the stability of the spirodiazaselenuranes and slows down the oxidative cyclization process. The selenium centre in the spiro compounds undergoes further oxidation to produce the corresponding selenurane oxides, which are stable at room temperature. Comparison of the glutathione peroxidase (GPx) mimetic activity of the compounds showed that the diaryl selenides having heterocyclic rings are significantly more active due to the facile oxidation of the selenium centre. However, the activity is reduced significantly for compounds having aliphatic substituents. In addition to GPx activity, the compounds also inhibit peroxynitrite-mediated nitration and oxidation reaction of protein and small molecules, respectively. The experimental observations suggest that the antioxidant activity is increased considerably upon substitution of the aromatic group with the benzylic/aliphatic substituents on the nitrogen atoms.
Asunto(s)
Antioxidantes/química , Antioxidantes/farmacología , Compuestos de Organoselenio/química , Compuestos de Organoselenio/farmacología , Antioxidantes/síntesis química , Cristalografía por Rayos X , Glutatión Peroxidasa/química , Modelos Moleculares , Compuestos de Organoselenio/síntesis química , Oxidación-Reducción/efectos de los fármacos , Ácido Peroxinitroso/antagonistas & inhibidores , Ácido Peroxinitroso/química , Fenoles , Selenio/química , Relación Estructura-ActividadRESUMEN
In this paper, the synthesis, characterization and glutathione peroxidase and peroxynitrite scavenging activities of a series of stable spirodiazaselenuranes are described. The spiro compounds were synthesized in good yields by oxidative cyclization of diaryl selenides bearing amide moieties. All the selenides and spiro derivatives were characterized by (1)H, (13)C and (77)Se NMR spectroscopy, mass spectral techniques and the structures of some of the spirodiazaselenuranes were confirmed by single crystal X-ray crystallography. The structures reveal that the selenium atom occupies the center of a distorted trigonal bipyramid core with two nitrogen atoms occupying the apical positions and two carbon atoms and the selenium lone pair occupying the equatorial positions. Mechanistic investigations indicate that the spirocyclization occurs via the formation of selenoxide intermediates. The new compounds were evaluated for their glutathione peroxidase (GPx) mimetic activity by using H(2)O(2) as a substrate and glutathione (GSH) as a co-substrate. It was found that the substituents attached to the nitrogen atom of the selenazole ring have a significant effect on the GPx activity. While the introduction of electron withdrawing groups such as -Cl, -Br etc. to the phenyl ring decreases the activity, the introduction of electron donating groups such as -OH, -OMe significantly enhances the GPx activity of both diaryl selenides and spirodiazaselenuranes. In addition to GPx activity, the selenides and spiro derivatives were studied for their ability to inhibit peroxynitrite (PN)-mediated nitration of bovine serum albumin (BSA) and oxidation of dihydrorhodamine 123. These studies indicate that the diarylselenides effectively inhibit the PN-mediated nitration and oxidation reactions by reacting with PN to produce the corresponding spirodiazaselenuranes.
Asunto(s)
Antioxidantes/química , Antioxidantes/síntesis química , Compuestos de Organoselenio/química , Compuestos de Organoselenio/síntesis química , Cristalografía por Rayos X , Depuradores de Radicales Libres/química , Glutatión Peroxidasa/química , Glutatión Peroxidasa/metabolismo , Modelos Moleculares , Estructura Molecular , Ácido Peroxinitroso/químicaRESUMEN
This article deals with the synthesis of 4-(2-hydroxyquinolin-3-yl)-6-phenyl-5,6-dihydropyrimidin derivatives (2a-f), on condensation with various aromatic aldehydes and ketones in aqueous ethanolic NaOH solution yielding the corresponding chalcones (3). These chalcones were further reacted with thiourea/urea in the presence of a base, which led to the formation of the titled derivatives (2a-f). The newly synthesized heterocyles were characterized by elemental analysis, FTIR, (1)HNMR, and electronic and mass spectral data. The compounds (2a and 2b) were evaluated for in vitro cyctotoxicity against human breast adenocarcinoma cell (MCF-7). In MTT cytotoxicity studies, both quinolinde derivatives were found most effective. The binding interaction behavior of the compound (2a) and (2d) with calf thymus-DNA (CT-DNA) was studied by electronic spectra, viscosity measurements, and thermal denaturation studies. On binding to CT-DNA, the absorption spectrum underwent bathochromic and hypochromic shifts. The binding constant (K(b)) observed 4.3 x 10(5) M(-1) for (2a), and 3.8 x 10(5) M(-1) for (2d) suggested that compound (2a) binds more strongly with base pairs than (2d).
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Chalconas/síntesis química , ADN/metabolismo , Hidroxiquinolinas/química , Pirimidinas/química , Agua/química , Absorción , Aldehídos/química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Chalconas/química , ADN/química , Femenino , Humanos , Cetonas/química , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Estructura Molecular , Desnaturalización de Ácido Nucleico , Espectroscopía Infrarroja por Transformada de Fourier , Análisis Espectral , Sales de Tetrazolio , Tiazoles , ViscosidadRESUMEN
The present article deals with the synthesis of 2-chloroquinoline-3-carbaldehyde [(2-hydroxy-1-naphthyl) methylene] hydrazone (CQCMH) (2a-c) and 2-chloroquinoline-3-carbaldehyde [4-(dimethylamino) benzylidene] hydrazone (CQCDBH) (3a-c) from quinoline derivatives under suitable experimental conditions. The synthesized compounds were characterized by elemental analysis, FTIR, (1)HNMR, and mass spectral data. The selected compounds were studied for interaction with calf thymus-DNA (CT-DNA) by electronic spectra, viscosity measurements as well as thermal denaturation studies. On binding to DNA, the absorption spectrum underwent bathochromic and hypochromic shifts. The binding constant (K(b)) had value of 2.3 x 10(3) M(-1) for (2a) and 2.5 x 10(4) M(-1) for (3a). The viscosity measurements indicated that the viscosity of sonicated rod like DNA fragments increased. The synthesized derivatives have been screened for antibacterial and antifungal activities.